Compositions and methods comprising energy absorbing compoundfs for follicular delivery

Abstract

The present invention provides compositions comprising energy (e.g., light) absorbing submicron particles (e.g., nanoparticles comprising a silica core and a gold shell) and methods for delivering such particles via topical application. This delivery is facilitated by application of mechanical agitation (e.g. massage), acoustic vibration in the range of 10 Hz-20 kHz, ultrasound, alternating suction and pressure, and microjets.

1 . A method of treating or ameliorating a follicular skin disease of a subject, the method comprising
 a) topically applying a formulation comprising a sub-micron particle comprising a light absorbing compound to a subject's skin;   b) facilitating delivery of said compound to a hair follicle, sebaceous gland, sebaceous gland duct, or infundibulum of the skin by mechanical agitation, acoustic vibration, ultrasound, alternating suction and pressure, or microjets; and   c) exposing said sub-micron particle to energy activation, thereby treating the follicular skin disease.   
     
     
         2 . The method of  claim 1 , wherein the submicron particle is a photoactive compound, photodynamic therapy (PDT) pro-drug or PDT drug. 
     
     
         3 . The method of  claim 1 , wherein the application of ultrasound energy is at a frequency in the range of 20 kHz to 500 kHz. 
     
     
         4 . A method of improving the appearance of enlarged pores in the skin of a subject, the method comprising
 a) topically applying a formulation of  claim 1  to a subject's skin;   b) facilitating delivery of said compound to a hair follicle, sebaceous gland, sebaceous gland duct, or infundibulum of the skin by mechanical agitation, acoustic vibration, ultrasound, alternating suction and pressure, or microjets; and   c) exposing said sub-micron particle to energy activation, thereby treating the follicular skin disease   
     
     
         5 . The method of  claim 1 , wherein the sub-micron particle is coated with PEG. 
     
     
         6 . The method of  claim 1 , wherein said particle is a nanoparticle comprising a silica core and a gold shell. 
     
     
         7 . The method of  claim 1 , wherein said nanoparticle is 150 nm in diameter. 
     
     
         8 . The method of  claim 1 , wherein said nanoparticle is a nanoshell. 
     
     
         9 . The method of  claim 6 , wherein the nanoparticle is coated with PEG. 
     
     
         10 . The method of  claim 1 , wherein energy activation is accomplished with a pulsed laser light that delivers light energy at a wavelength that is absorbed by the particle. 
     
     
         11 . The method of  claim 1 , wherein said skin is prepared for the method by heating, by removing the follicular contents, and/or by epilation. 
     
     
         12 . The method of  claim 9 , wherein the follicular contents are removed by a method comprising contacting the follicle pore with adhesive polymers. 
     
     
         13 . The method of  claim 1 , wherein said topically applied sub-micron particles are wiped from the skin prior to energy activation. 
     
     
         14 . The method of  claim 1 , wherein said topically applied sub-micron particles are wiped from the skin with acetone. 
     
     
         15 . The method of  claim 1 , wherein said follicular skin disease is acne vulgaris. 
     
     
         16 . The method of  claim 1 , wherein energy activation is carried out by irradiation of the skin with a laser. 
     
     
         17 . The method of  claim 1 , wherein the ultrasound energy has a frequency in the range of 20 kHz to 500 kHz. 
     
     
         18 . The method of  claim 1 , wherein where the skin is heated before, during, or after topical application to about 42° C. or to a temperature sufficient to assist in follicular delivery. 
     
     
         19 . The method of  claim 16 , wherein the heating is accomplished via ultrasound. 
     
     
         20 . The method of  claim 16 , wherein the heating is not sufficient to cause pain, tissue damage, burns, or other heat-related effects in the skin. 
     
     
         21 . A method for permanently removing lightly pigmented or thin hair of a subject, the method comprising
 a) topically applying a light-absorbing compound to the skin of a subject, and   b) exposing said compound to energy activation, thereby permanently removing said hair.   
     
     
         22 . The method of  claim 21 , further comprising
 epilating hair from a follicle of the subject prior to topical application of the light-absorbing compound.   
     
     
         23 - 26 . (canceled) 
     
     
         27 . A method of facilitating delivery of a light absorbing compound to a target volume within the skin of a subject, the method comprising
 a) topically applying a formulation comprising a light absorbing compound to a subject's skin to deliver the compound to a reservoir within the skin;   b) facilitating delivery of said compound to a target volume within the skin of the subject by irradiating the skin with a first series of light pulses; and   c) exposing said light absorbing compound to a second series of light pulses to heat the compound and thermally damage the target volume to achieve a therapeutic effect.   
     
     
         28 . A method of facilitating delivery of a light absorbing compound to a target volume within the skin of a subject, the method comprising
 a) topically applying a formulation comprising a light absorbing compound to a subject's skin;   b) facilitating delivery of said compound to a reservoir in the skin by mechanical agitation;   c) facilitating delivery of said compound to a target volume within the skin by applying a train of low-energy laser pulses each pulse lasting for a microsecond or less to drive the material into the target volume; and   d) exposing said light absorbing compound to a second series of low-energy laser pulses to heat the compound and thermally damage the target volume to achieve a therapeutic effect.   
     
     
         29 - 34 . (canceled) 
     
     
         35 . A composition comprising a cosmetically acceptable carrier and a plurality of plasmonic nanoparticles in an amount effective to induce thermomodulation in a target tissue region with which the composition is topically contacted. 
     
     
         36 - 49 . (canceled) 
     
     
         50 . A method for performing targeted ablation of a tissue to treat a mammalian subject in need thereof, comprising the steps of i) topically administering to a skin surface of the subject the composition of  claim 35 ; ii) providing penetration means to redistribute the plasmonic particles from the skin surface to a component of dermal tissue; and iii) causing irradiation of the skin surface by light. 
     
     
         51 - 53 . (canceled) 
     
     
         54 . The composition of  claim 35 , further comprising an effective amount of sodium dodecyl sulfate, wherein the nanoparticles have an optical density of at least about 1 O.D. at a resonance wavelength of about 810 nanometers or 1064 nanometers, wherein the plasmonic particles comprise a silica coating from about 5 to about 35 nanometers, wherein the acceptable carrier comprises water and propylene glycol. 
     
     
         55 . A system for laser ablation of hair or treatment of acne comprising the composition of  claim 35  and a source of plasmonic energy suitable for application to the human skin.